课题基金 / 基金详情

Caenorhabditis elegans infection model for Coxiella burnetii

Caenorhabditis elegans infection model for Coxiella burnetii
伯内氏柯克斯体的秀丽隐杆线虫感染模型
批准号:
9221965
负责人:
Michael F Minnick
金额:
$18.13万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-02-15 至 2019-01-31

项目摘要

项目成果

Michael F Minnick的其他基金

相似基金

相关文献

中文摘要
翻译

英文摘要
 DESCRIPTION (provided by applicant): Coxiella burnetii is an extremely infectious, intracellular bacterium that causes Q fever in humans and is classified as a select agent. Q fever typically presents as a debilitating, flu-like illness accompanied by pneumonia or hepatitis, but in a minority of cases a severe, chronic infection occurs with life-threatening endocarditis as the predominant manifestation. Little is known about Coxiella's virulence determinants or how the bacterium subverts the host cell, despite the central role for these factors and activities in the pathogen's survival. Our overall goals are to identify novel virulence determinants of C. burnetii and characterize the host's innate immune response against the bacterium during infection. To that end, we recently developed a novel animal model for Coxiella infection in Caenorhabditis elegans. When C. elegans nematodes feed on C. burnetii, the intestines become persistently colonized. Moreover, infection significantly decreases the worm's lifespan and produces a visible and pronounced pathology (deformed anal region or DAR). Previous reports showing that virulence factors identified in the C. elegans infection model are similarly utilized in higher-order hosts and that signaling pathways of C. elegans' innate immune response (IR) against pathogens are conserved in higher eukaryotes, underscores the value of this model for investigating human pathogens. We hypothesize that the C. elegans model of infection can be utilized in a high-throughput fashion to identify novel virulence factors of Coxiella and to analyze effectors of the worm's innate immune response against this enigmatic bacterium. To address the hypothesis, Aim 1 will screen a library of C. burnetii Himar1 TnA7 mutants for reduced fitness in C. elegans to identify potential virulence factors. Once identified, the corresponding Coxiella genes will be investigated using molecular Koch's postulates to verify their role in potentiating virulence. TNSeq will also be done to analyze the contribution of every mutagenized gene in the Coxiella library to bacterial fitness over the course of infection. I Aim 2, we will analyze the "infection-specific" transcriptome of C. elegans by RNASeq to identify innate IR effectors against C. burnetii. In Aim 3, we will investigate the functionality of these innate IR effectors using a combination of RNAi and mutant strains of C. elegans to investigate host susceptibility to a Coxiella infection, relative to wild-type nematodes. In the end, this stud will significantly move the field forward by: a) identification and analysis of novel Coxiella virulence determinants, b) providing a new animal model of C. burnetii infection that will facilitae screening for virulence factors and other desirable phenotypes, and c) characterizing potentially novel, innate IR effectors that are utilized by a host to counter the pathogen.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
A CsrA-Binding, trans-Acting sRNA of Coxiella burnetii Is Necessary for Optimal Intracellular Growth and Vacuole Formation during Early Infection of Host Cells.
伯内氏立克次体的 CsrA 结合、反式作用 sRNA 对于宿主细胞早期感染期间的最佳细胞内生长和液泡形成是必要的。
DOI: 10.1128/jb.00524-19
发表时间: 2019
期刊: Journal of bacteriology
影响因子: 3.2
作者: [Wachter,Shaun, Bonazzi,Matteo, Shifflett,Kyle, Moses,AbrahamS, Raghavan,Rahul, Minnick,MichaelF]
通讯作者: Minnick,MichaelF
Targetomes of infection-specific small RNAs of Bartonella bacilliformis
  • 批准号:
    10414729
  • 项目类别:
  • 资助金额:
    $7.4万
  • 财政年份:
    2022
  • 负责人:
    Michael F Minnick
  • 依托单位:
Targetomes of infection-specific small RNAs of Bartonella bacilliformis
  • 批准号:
    10606530
  • 项目类别:
  • 资助金额:
    $7.4万
  • 财政年份:
    2022
  • 负责人:
    Michael F Minnick
  • 依托单位:
Small RNAs of Bartonella bacilliformis; the agent of Carrion's disease in humans
  • 批准号:
    9227738
  • 项目类别:
  • 资助金额:
    $22.7万
  • 财政年份:
    2016
  • 负责人:
    Michael F Minnick
  • 依托单位:
Role of surface proteins in sand fly colonization by Bartonella bacilliformis
  • 批准号:
    8303852
  • 项目类别:
  • 资助金额:
    $21.23万
  • 财政年份:
    2012
  • 负责人:
    Michael F Minnick
  • 依托单位:
海外基金